New Depression Drug Offers Hope

Traditional depression meds don’t work for everyone—but this new drug could fill the gap.

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Posted Sep. 6, 2013 at 12:01 AM
Updated Sep 6, 2013 at 11:25 PM

Posted Sep. 6, 2013 at 12:01 AM
Updated Sep 6, 2013 at 11:25 PM

Depression is not pretty: It erodes your appetite for life, energy, self-esteem, concentration, and supplants those with hopelessness. Yet of the 10 percent of the population that suffers from depression, 30 to 40 percent are not helped by traditional antidepressants such as selective serotonin reuptake inhibitors (SSRIs).
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But a new drug, cousin of the anesthetic and street drug ketamine and called by the geeky term GLYX-13, may be the best new alternative, according to a 2013 animal study at Northwestern University in Evanston, Ill. What’s more, the drug appears to improve learning and memory, and lessen pain.
How GLYX-13 Works
GLYX-13, like ketamine, affects N-methyl-D-aspartate (NMDA), one of the 40 to 60 glutamate receptors in the brain, explains senior study author and molecular neurobiologist Joseph Moskal, biomedical engineering research professor and director of the Falk Center for Molecular Therapeutics at Northwestern. “NMDA plays the biggest role in modulating normal learning processes,” he says.
Glutamate is one of the most prevalent neurotransmitters in the brain, adds psychiatrist Dr. Prakash Masand, Chairman and CEO of Global Medical Education, an online medical education resource. “The thinking is that [in depression] there is an abnormality in the connection between the glutamate neurons, and that GLYX-13 corrects that abnormal connection.” That disconnection may also be true for other mental disorders such as schizophrenia, autism and attention deficit hyperactivity disorder (ADHD), fueling hope that GLYX-13 may help those conditions as well, says Masand, who also teaches at Columbia University in New York City.
Although ketamine, the street drug, acts as a long-lasting antidepressant in clinical trials, it has toxic side effects. “If you give animals [trapped in water] ketamine, they dive around, hallucinating and defecating,” says Moskal. “But if you give animals GLYX-13, right away they swim and swim. [Depressed] animals without GLYX-13 just float and quit.”
How GLYX-13 is Different from other Antidepressants
SSRIs work on an entirely different system--the serotonergic, or serotonin, system--than GLYX-13. Serotonin is a neurotransmitter that, when low, affects mood, particularly depression and anxiety. But no one knows why SSRIs work only on some, not all, depressed people.
Perhaps the most remarkable difference between GLYX-13 and other antidepressants is that GLYX-13 works within 24 hours, says Masand. Current antidepressants take two to four weeks to have an effect and come with unpleasant side effects, such as reduced sexual desire, dry mouth and insomnia, among others.
“We have not seen any conspicuous side effects in single-dose [human] studies of GLYX-13,” says Moskal. “But we are just now doing [human] studies with repeated doses so we can’t say yet that that will hold up.”
Moskal predicts that the drug will be available in injectable form by 2015 or 2016. The effects of one injection should last a week.
“We have also started a phase 1 toxicity study on an oral compound, NRX 1074” says Moskal. “So we may be able to give GLYX-13 in oral form, also probably once a week.”
Most exciting is that GLYX-13 is helping scientists understand how depression—and perhaps other mental disorders—work, says Moskal: “We’re assuming that not everyone will be cured with GLYX-13 because some people respond to SSRIs, which work through a different mechanism. But we’re defining psychological problems that all [appear to] have a NMDA [related] component. If that’s true, then maybe GLYX- 13 may be effective for those as well.”
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